PROJECT ABSTRACT Maternal, fetal and infant health relies on the cross-talk between the mother, placenta and fetus. The placenta is key to pregnancy success as it is responsible for the exchange of all nutrients, gases and wastes between the maternal and fetal circulations and importantly it orchestrates maternal adaptations to pregnancy by secreting many hormones and peptides into the maternal circulation. Surprisingly there are no robust, non- invasive methods in clinical practice to assess placental health across gestation in pregnant women. We hypothesize that the maternal plasma miRnome and maternal circulating leukocyte DNA methylome reflect dynamic changes in the placental transcriptome, miRnome and DNA methylome that correlate with placental function and health and that these can be assessed non-invasively across gestation. We will use miRNA sequencing, RNA sequencing and DNA methylation arrays to create molecular profiles in paired maternal blood and placental samples at multiple time points across gestation. We will leverage samples and extensive data from existing cohorts of pregnant women in Adelaide, Australia and Atlanta, GA. We will primarily focus on samples from women who had uncomplicated pregnancies but a side aim will be to compare the profiles in women with uncomplicated pregnancies with those of women who developed preeclampsia. We will incorporate into our bioinformatics and biostatistical analyses clinical and lifestyle data such as maternal diet, BMI, smoking, fetal sex, as well as over 50 biomarkers already measured in blood at 15 weeks gestation that could influence the epigenome. We will include all available factors that may contribute to molecular changes in the placenta and maternal circulation and thereby to pregnancy outcome in our analyses. Uterine and umbilical artery Doppler studies and fetal size at 12, 20 and 24 weeks gestation and birth weight and length will be used to assess the relationships between our omic analyses and placental development and function. Hence, we will provide a non-invasive profile in maternal blood that reflects placental development and function in real time. Our distinct cohorts will additionally allow us to identify racial differences in the placental transcriptome, miRnome and methylome that may provide insights into population disparities in pregnancy outcomes.